Healthy physiologic function is characterized by the complex interaction of multiple control systems and feedback loops that enable a subject to rapidly adapt to the internal and external stresses of everyday life. This dynamic interplay of multiple regulatory mechanisms is key to the ability to maintain internal equilibrium and good health in older adults. Cumulative declines across multiple physiologic systems and regulatory mechanisms have been hypothesized to be a major pathway to frailty in older adults. The overall goal of this project is to investigate the role of dysregulation of cardiovascular dynamics, as assessed by measures of heart rate (HR) variability and complexity, in frailty and disability, and to explore how such dysregulation may interact with other physiologically-related systems to exacerbate the risk for adverse outcomes. Specifically, we will conduct secondary data analyses using data from 525 women 3 age 65 from the Women's Health and Aging Study I, to test the following hypotheses: (1) Cross-sectionally, reduction in HR variability and complexity are independently associated with: (a) decreased exercise-tolerance, (b) impaired cardio-acceleration in response to isometric and isokinetic stressors (c) frailty status, (d) and severity of disability; (2) Longitudinally, reduction in HR variability and complexity are predictive, independent of chronic diseases, of onset and progression of frailty and disability, and mortality; and (3) There are interactions between reduction in HR variability and complexity and impairment in other physiologic parameters of the cardiopulmonary system, particularly hemoglobin, FEV1, and atherosclerosis (measured by the ankle-arm index), vis-a-vis risk of frailty, disability, and mortality. Inferences will ultimately be based on regression models within the generalized linear model framework. Proportional hazards models will be used for time-to-event analysis. Interactions will be assessed through standard regression techniques, and by sequence analysis using "logic regression". Potential practical implications of this study include: (a) the identification of clinically relevant interactions between physiologic systems and threshold associations, which might lead to the development of methods to identify those at risk of frailty, and (b) development of multifactorial interventions targeting simultaneous impairments in multiple physiologic systems for prevention of frailty and disability in older adults.